On the encapsulation of Olsalazine by β-cyclodextrin: A DFT-based computational and spectroscopic investigations

Abstract

In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and β-Cyclodextrin (β-CD) was examined experimentally and computationally. Experimentally, employing the UV-Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi-Hilderbrand approach demonstrated that OLZ can form supramolecular inclusion complex with β-CD with stoichiometric ratio of 1:1. Furthermore, these results revealed that the formation of OLZ: β-CD complexes exhibited insignificant pH dependency in the range 5-8 with an average binding constant (K_b) of approximately 1×10³M^-1. Computationally, geometry optimization of 1:1 OLZ: β-CD complexes was performed employing the ONIOM (DFT((ωB97XB)/6-31+G(d)),SQM(PM3)) approach. Obtained results demonstrated that OLZ: β-CD complex is stabilized by the formation of intermolecular hydrogen bonds with an average length of approximately 1.8Å. Additionally, the stability of OLZ: β-CD complex was demonstrated employing ADMP molecular dynamic simulations over a timeframe of 500fs. The molecularity of the supramolecular host-guest interaction between OLZ and β-CD is presented and interpreted in the essence of TD-DFT and molecular orbitals analyses.

Keywords: Computational methods; DFT; Encapsulation; Inclusion complexes; ONIOM; Olsalazine; TD-DFT; UV–vis spectroscopy; β-Cyclodextrin.